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Dapsone-induced methemoglobinemia: "Saturation gap"-The key to diagnosis.
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PMID:  24574600     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
Two cases of Acquired Methemoglobinemia are presented. The significance of a high index of suspicion for diagnosisis emphasized, especially in the presence of a "saturation gap". The various causes of acquired methemoglobinemia are enumerated and the management reviewed.
Authors:
Shivinder Singh; Navdeep Sethi; Sushmitha Pandith; Gouri Shankar Ramesh
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of anaesthesiology, clinical pharmacology     Volume:  30     ISSN:  0970-9185     ISO Abbreviation:  J Anaesthesiol Clin Pharmacol     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-02-27     Completed Date:  2014-02-27     Revised Date:  2014-03-03    
Medline Journal Info:
Nlm Unique ID:  9516972     Medline TA:  J Anaesthesiol Clin Pharmacol     Country:  India    
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Languages:  eng     Pagination:  86-8     Citation Subset:  -    
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Journal Information
Journal ID (nlm-ta): J Anaesthesiol Clin Pharmacol
Journal ID (iso-abbrev): J Anaesthesiol Clin Pharmacol
Journal ID (publisher-id): JOACP
ISSN: 0970-9185
ISSN: 2231-2730
Publisher: Medknow Publications & Media Pvt Ltd, India
Article Information
Copyright: © Journal of Anaesthesiology Clinical Pharmacology
open-access:
Print publication date: Season: Jan-Mar Year: 2014
Volume: 30 Issue: 1
First Page: 86 Last Page: 88
PubMed Id: 24574600
ID: 3927300
Publisher Id: JOACP-30-86
DOI: 10.4103/0970-9185.125710

Dapsone-induced methemoglobinemia: “Saturation gap”—The key to diagnosis
Shivinder Singhaff1
Navdeep Sethiaff1
Sushmitha Pandithaff1
Gouri Shankar Rameshaff1
Department of Anesthesiology and Critical Care, Armed Forces Medical College, Pune, Maharashtra, India
Correspondence: Address for correspondence: Dr. Col. Shivinder Singh, Department of Anesthesiology and Critical Care, Armed Forces Medical College, Solapur Road, Pune - 410040, Maharashtra, India. E-mail: sshivinder@hotmail.com

Introduction

Dapsone is a drug that is used in the treatment of leprosy and acne vulgaris owing to its immunosuppressive effects. Long-term administration of dapsone at standard doses (100 mg/day) results in methemoglobinemia in about 15% of patients.[1] Classically, low pulse oximeter readings are associated with hypoxia, however methemoglobinemia is an important albeit uncommon cause.[2] We report two cases of dapsone-induced methemoglobinemia with evident cyanosis, one in the emergency department and the other in a patient undergoing elective splenectomy.


Case Report
Case 1

A 36-year-old woman was diagnosed with immune thrombocytopenic purpura in July 2012 and started on oral prednisolone and dapsone 100 mg/day. About 3 months later, she was admitted to the hospital with fatigue, headache, arthralgia, and severe dyspnea. Physical examination was normal except for peripheral cyanosis. She had a platelet count of 1,000/cmm, hemoglobin of 7.9 gm%. SpO2 on room air was 84%, respiratory rate was 52/min. Owing to intolerance for non-invasive ventilation (NIV) and low saturation, the patient was intubated and ventilated.

Arterial blood gas (ABG) analysis revealed a pH of 7.43, PaO2-180 mmHg, PaCO2-32 mmHg, SaO2-99.1% on oxygen by facemask. In view of history of dapsone intake, cyanosis, low SpO2 with normal PaO2 and SaO2(on ABG) a diagnosis of methemoglobinemia was considered and dapsone was stopped, however, the facility for methemoglobin (methHb) estimation was not available. After 48 hrs of mechanical ventilation, she improved symptomatically and was extubated following a weaning trial. She was shifted to high dependency unit with oxygen 5l/min. The SpO2 continued to remain low ranging from 88-92% over the next 3 days though the SaO2 was normal. As the patient remained clinically stable, no further intervention was carried out and she made an uneventful recovery.

Case 2

An 8-year-old girl, a known case of immune thrombocytopenic purpura, with treatment history of oral prednisolone 20 mg/day and dapsone 50 mg/day since 1 year, was planned for laparoscopic splenectomy.

Pre-operative assessment revealed cushingoid features, skin discoloration all over the body and splenomegaly [Figure 1].

She had a platelet count of 20,000/cmm but the other hematological variables were normal. Oxygen saturation on room air was 88%. During maintenance of general anesthesia with a 60:40 (nitrous oxide:oxygen) gas oxygen ratio, the SpO2 rose to 92%. Vital signs, physical examination including bilateral air entry was normal, end tidal carbon dioxide and airway pressures were unremarkable. Intraoperative ABG analysis revealed a PaO2 of 260 mmHg, pH 7.40, PaCO2 38 mmHg, HCO3 22.4 meq.l-1 and SaO2 of 99%. Filter paper test done on the patient's blood comparing it with blood from a normal patient [Figure 2] which showed that the patient's blood remained dark even after exposure to atmospheric oxygen.

Deoxyhemoglobin can be distinguished from methHb by this simple bedside test. By placing 1 or 2 drops of the patient's blood on a white filter paper: Deoxyhemoglobin brightens after exposure to atmospheric oxygen, but methHb does not change color.[2]

She was transferred to the pediatric intensive care unit (ICU) with oxygen therapy by polymask at 5 l/min, as SpO2 remained 86% on room air. Blood analysis showed methHb levels of 28.6%. Dapsone was stopped and the patient remained asymptomatic with supplemental oxygen by facemask. As the methHb levels were less than 30% and the patient was stable, therapy with methylene blue was not considered.


Discussion

The majority of cases of acquired methemoglobinemia described in literature have resulted from exposure to exogenous oxidizing agents like nitrites used as preservatives in food or as a deliberate poison,[3, 4] amyl nitrate used as a recreational agent,[5, 6] abuse of paint thinner by addicts,[7] intake of nitrate containing vegetables[8] use of EMLA cream,[9, 10] and Dapsone intake.[11, 12]

The peak plasma concentrations of Dapsone are reached within 2-8 hours after ingestion. The mean elimination half-life varies from 10 to up to 80 hours in overdose situations. In healthy erythrocytes, cellular enzymes rapidly reduce any naturally occurring methHb. An exposure to oxidative medications can overcome these reducing enzymes thus causing an accumulation of methHb.[2] The role of nitric oxide (NO) in the pathophysiology of methemoglobinemia is also being studied.[13] The presence of methHb in the erythrocyte prevents the binding of oxygen as also increases the affinity of normal hemoglobin molecules for oxygen, shifting the oxygen dissociation curve to the left, thus further decreasing oxygen delivery to the tissues.[2, 14]

The symptoms and signs are proportional to the level of methemoglobin. Asymptomatic, if less than 15%; cyanosis in levels above15%; headache, dyspnea, nausea, tachycardia, and weakness in levels above 20%; coma sets in above 45%, and a high mortality rate is associated with levels above 70%.[15]

While cyanosis is a pointer to the diagnosis, varying oxygen saturation seen with pulse oximetry often confuses the issue. Standard colorimetric pulse oximeters show falsely low readings in mild toxicity and falsely high readings in severe toxicity by giving a constant reading in the low 80s in the presence of methHb.[2] On the other hand, most arterial blood gas analyzers calculate the oxygen saturation based on the PaO2(which is a measure of the dissolved oxygen in plasma) and so give false high values. Therefore, a “saturation gap” between the recorded saturation from the pulse oximeter as compared to the reported saturation in the arterial blood gas may be detected[16] and in the presence of a high index of suspicion, may be the key to diagnosis, especially in the resource limited setting.[3]

A pulse oximeter is now available that uses eight wavelengths of light and can accurately measure both methHb and carboxyhemoglobin (the Rainbow-SET Rad-57 Pulse CO-Oximeter, Masimo, Inc., Irvine, CA). It is capable of giving continuous readings of methHb level at the bedside.[17]

Management consists of removing the offending agent, high-dose oxygen, and intravenous methylene blue. Methylene blue (1-2 mg.kg−1) administered intravenously over a period of 3-5 minutes (contraindicated in G6PD deficiency) produces a rapid conversion of meth Hb to hemoglobin. Its use is recommended in all patients with meth Hb levels greater than 30% or in symptomatic patients at lower levels. Exchange transfusion and hyperbaric oxygen may also be considered for severe or refractory cases.[18]

These two cases emphasize the importance of good history taking, knowledge of drugs likely to cause methemoglobinemia and a high index of suspicion especially in the presence of a “saturation gap”.


Notes

Source of Support: Nil

Conflict of Interest: None declared.

References
1. Coleman MD,Rhodes LE,Scott AK,Verbov JL,Friedmann PS,Breckenridge AM,et al. The use of cimetidine to reduce dapsone-dependent methaemoglobinaemia in dermatitis herpetiformis patientsBr J Clin PharmacolYear: 19923424491389948
2. Steiner IP,Nichols DN. A case of dapsone-induced cyanosis in the emergency departmentIsr J Emerg MedYear: 20066103
3. Nabukeera-Barungi N,Mworozi E. Sudden onset methaemoglobinaemia in a previously well Ugandan child: A case report and literature reviewPan Afr Med JYear: 2012114922593785
4. Su YF,Lu LH,Hsu TH,Chang SL,Lin RT. Successful treatment of methemoglobinemia in an elderly couple with severe cyanosis: Two case reportsJ Med Case RepYear: 2012629022967308
5. Sheena Y,Baston EL,Downs A,Chester DL. A sticky situation: Methaemaglobinaemia in a hand trauma patientBMJ Case RepYear: 201212012
6. Hall A,Stessel B,Bergmans D,Schnabel R. Two cases of acquired methemoglobinemiaActa Anaesthesiol BelgYear: 2012639710023136811
7. Singh R,Vinayagam S,Vajifdar H. Methemoglobinemia as a result of accidental lacquer thinner poisoningIndian J Crit Care MedYear: 20121644722557834
8. Martinez A,Sanchez-Valverde F,Gil F,Clerigué N,Aznal E,Etayo V,et al. Methemoglobinemia induced by vegetable intake in infants in north SpainJ Pediatr Gastroenterol NutrYear: 201356573723287806
9. Schmitt C,Matulic M,Kervégant M,Tichadou L,Boutin A,Glaizal M,et al. Methaemoglobinaemia in a child treated with Emla(®) cream: Circumstances and consequences of overdoseAnn Dermatol VenereolYear: 2012139824723237281
10. García-Saura PL,Serrano Álvarez C. Methaemoglobinaemia in a healthy patient after using topical anaesthetic cream, for laser depilationRev Esp Anestesiol ReanimYear: 2012
11. Ash-Bernal R,Wise R,Wright SM. Acquired methemoglobinemia: A retrospective series of 138 cases at 2 teaching hospitalsMedicine (Baltimore)Year: 2004832657315342970
12. Stichtenoth D. Lip cyanosis in dapsone therapy: Should the dosage be reduced?MMW Fortschr MedYear: 20121543222642026
13. Sanyal T,Chakraborty S. Multiscale analysis of hypoxemia in methemoglobin anemiaMath BiosciYear: 20132411678023201463
14. Burke MD,DelGiacco E,Curran AL,Savior DC. Besa ECMethhemoglobinemiaEmedicineUpdated: Jun 3, 2013 Accessed on 13 Dec 2013 Available from: http://www.emedicine.com/Emerg/topic313.htm.
15. Curry S. MethemoglobinemiaAnn Emerg MedYear: 198211214217073040
16. Barker SJ,Tremper KK,Hyatt J. Effects of methemoglobinemia on pulse oximetry and mixed venous oximetryAnesthesiologyYear: 19897011272912291
17. Annabi EH,Barker SJ. Severe methemoglobinemia detected by pulse oximetryAnesth AnalgYear: 2009108898919224799
18. Mycyk MB. Longo DL,Fauci AS,Kasper DL,Hauser SL,Jameson JL,Loscalzo JPoisoning and drug overdosageHarrison's OnlineYear: 201218th edNew YorkMcGraw-Hill

Figures

[Figure ID: F1]
Figure 1 

Cushingoid features with cyanosis



[Figure ID: F2]
Figure 2 

Filter paper test



Article Categories:
  • Case Report

Keywords: Acquired methemoglobinemia, dapsone, saturation gap.

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